Perel E, Daniilescu D, Kharlip L, Blackstein M, Killinger D W
Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
J Steroid Biochem. 1988 Apr;29(4):393-9. doi: 10.1016/0022-4731(88)90248-8.
Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue.
研究了具有孕激素或雄激素活性的皮质醇和类固醇，以确定这些类固醇对人培养乳腺癌细胞中雄烯二酮（A）转化为雌酮（E1）的影响。皮质醇（10^(-6)M）刺激了两种雌激素无反应细胞系（MD、DM）和一种雌激素反应细胞系（MCF7）中的芳香化酶活性，在汇合时出现最大刺激。皮质醇抑制了MCF7细胞的复制，但不抑制MD和DM细胞的复制。双氢睾酮、雄酮和5α-雄烷二酮（10^(-6)M）在基础和皮质醇刺激条件下，抑制A转化为E1的幅度大于90%。孕酮（10^(-6)M）对芳香化酶活性无影响，而孕激素R5020（10^(-6)M）产生了30%的抑制作用。同样具有孕激素活性的合成代谢类固醇19-去甲睾酮和19-去甲雄烯二酮以剂量依赖方式抑制A转化为E1，在10^(-6)M时抑制率为90%。具有雄激素和孕激素活性的药物达那唑（10^(-6)M）抑制E1形成30%。在相同条件下，已知的芳香化酶抑制剂4-羟基雄烯二酮（10^(-6)M）使E1形成减少超过90%，而氨鲁米特（10^(-6)M）仅引起25%的抑制。这些研究表明，内源性和外源性类固醇可能在调节培养的乳腺癌细胞中雄激素前体向雌激素的局部形成方面具有显著作用。这种对雌激素形成的影响可能是乳腺组织生物学反应的一个因素。
